Search

Cyclin-dependent kinase 5 (Cdk5) plays a critical role during neurodevelopment, synaptic plasticity, and neurodegeneration. Cdk5 activity depends on association with neuronal proteins p35 and p25, a proteolytic product of p35. Cdk5 regulates the actin cytoskeletal dynamics that are essential for neuronal migration, neuritic growth, and synaptogenesis. However, little is known about the interaction of actin and Cdk5 and its effect on neuronal Cdk5 activity. In a previous study, we observed that Cdk5/p35 activity is negatively correlated with co-immunoprecipitated F-actin (filamentous actin) amounts in the mouse brain, and suggested that F-actin inhibits the formation of the Cdk5/p35 complex [Journal of Neuroscience (2008) vol. 28, p. 14511]. The experiments reported here were undertaken to elucidate the relationship between actin and the formation of the Cdk5/p35 complex and its activity. Instead of an F-actin-mediated inhibition, we propose that G-actin (globular actin) in the F-actin preparations is responsible for inhibiting Cdk5/p35 and Cdk5/p25 kinase activity. We found that F-actin binds to p35 but not p25 or Cdk5. We have shown that G-actin binds directly to Cdk5 without disrupting the formation of the Cdk5/p35 or Cdk5/p25 complexes. G-actin potently suppressed Cdk5/p35 and Cdk5/p25 activity when either histone H1 or purified human tau protein were used as substrates, indicating a substrate-independent inhibitory effect of G-actin on Cdk5 activity. Finally, G-actin suppressed the activity of Cdk5 immunoprecipitated from wild type and p35-deficient mouse brain, suggesting that G-actin suppresses endogenous Cdk5 activity in a p35-independent manner. Together, these results suggest a novel mechanism of actin cytoskeletal regulation of Cdk5/p35 activity. [ABSTRACT FROM AUTHOR]

The morale inventory in this paper is composed of 11 miniature scales designed to measure attitudes related to various phases of morale. The scales are internally relatively homogeneous, and in spite of their brevity provide satisfactory retest reliabilities. The scales include items relating to personal morale of the emotional sort; confidence in the favorable outcome of the war; distrust of news sources; willingness to have civil liberties and social reforms suspended during the war; support of the war; and aggression toward the enemy, foreign-born in this country, our allies, our government and laws, and people in general. Intercorrelations of the scales indicate that morale is by no means a unitary variable. The correlations are generally low, although some interesting relationships come to light. Studies of a sample of the adult population of Minneapolis have shown that attitudes which would be considered solely on rational grounds to be favorable to the furtherance of the War effort do not always tend to go together. It has been found, for example, that favorable attitudes toward our allies and our government and laws are negatively correlated with expressions of aggression toward the enemy and toward aliens in this country. Aggressive attitudes, whether favorable or unfavorable to the war effort tend to be associated. Personal morale and optimism as to the course of the war appear to be relatively independent of other attitudes. [ABSTRACT FROM AUTHOR]